The area of asymmetric synthesis has grown in importance due to the increased emphasis on evaluation and marketing of the active enantiomer of a drug as opposed to its corresponding racemate. Hence, asymmetric synthetic approaches to a variety of chiral, biologically active molecules as well as their structural analogs are of much interest to the chemist and the pharmaceutical industry. The goal of the PI's research program is to develop new and useful methodology for the asymmetric synthesis of a variety of biologically active molecules. The first goal of this proposal is to develop methods for the preparation of a number of functionalized chiral nonracemic hydroxysulfones and hydroxy phosphonates. Bakers' yeast reductions of appropriate carbonyl precursors or the lipase catalyzed resolution of racemic alcohols will both be carefully examined as potential routes for the generation of these chiral synthons in high optical purities and with the desired configuration. The second goal of the proposal is to demonstrate the synthetic utility of these chiral intermediates. In this context, it is important to mention that intermediates having the sulfonyl and phosphonate groups are well known for their synthetic versatility. It is proposed to develop some new methodology that exploits the unique chemistry of these chiral synthons. More specifically, the intramolecular cyclization reactions of some unsaturated acyl sulfones and acyl phosphonates have much synthetic potential and need to be investigated. Finally, it is proposed to synthesize some known biologically active macrolides such as pyrenophorin and lasiodiplodin using intermediates generated from this work.